Use of the oncolytic enzyme, L-asparaginase, demonstrated that deprivation of a non-essential amino acid could have lethal repercussions on tumor cells. This Laboratory is exploring alternate means of achieving such deprivations by inhibiting L-asparagine synthetase, L-asparaginyl-tRNA synthetase, and stimulating endogenous L-asparaginase activities. Orthodox drugs and intermediary metabolites are among the agents being examined in a systematic way for such actions. In addition, inasmuch as L-glutamine is the ordinary source of the nitrogen of L-asparagine, we are exploring a select number of powerful L-glutamine antagonists for their perturbation of L-asparagine metabolism. Lastly, a small number of new oncolytic enzymes are being subjected to therapeutic and toxicologic testing.